Human and rat natural killer (NK) cells have been studied in detail. NK activity in these species has been shown to be mediated by large granular lymphocytes (LGL) and LGL have also been detected in a variety of other species. Rat LGL were shown to share surface markers with both T cells and macrophages and the number of these cells was appreciably increased in nude rats. Clones of cultured mouse NK cells have been produced and these also share some antigens with T cells. The mechanism of augmentation of rat NK activity by interferon (IFN) was analyzed and shown to involve increases in target binding by LGL and also increased lytic activity. In contrast to boosting of NK activity, IFN had no effect on cytotoxicity by immune mouse T cells. Depression of NK activity by various agents was shown to be due either to altered regulation or to reduction in the number of effector cells. A role for proteases and not for reactive oxygen species in the mechanism of NK activity has been demonstrated. NK cells have also been shown to produce IFN in response to a variety of stimuli. NK cells were reactive against primary mouse mammary tumors as well as against tumor cell lines and further evidence has been obtained for an in vivo role of NK cells, including their possible activity in immune surveillance.